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Biomedical subjects

J Saal

Publications and source records attributed to J Saal.

At least 19 recordsLinked to original sources
PubMed2000

Immunoadsorption onto protein A induces remission in severe systemic lupus erythematosus.

BACKGROUND: Reduction of pathological autoantibodies and circulating immune complexes can be useful in the treatment of autoimmune disease. Plasmapheresis has been shown to reduce autoantibody levels in systemic lupus erythematosus (SLE), but its effect on patients' outcome was not better compared with conventional immunosuppression in the past. AIM OF THE STUDY: Immunoadsorption as a selective extracorporeal immunoglobulin elimination technique was evaluated as rescue therapy in patients suffering from SLE. METHODS: Eight patients with severe, therapy-resistant SLE underwent immunoadsorption onto protein A sepharose without concomitant immunosuppressants. RESULTS: Remission of the disease was achieved in seven patients. Therapy had to be stopped in one patient because of side-effects. The best results were obtained when immunoadsorption was carried out daily, without supplementary intravenous immunoglobulin therapy. Oral cyclophosphamide for 3-6 months during follow-up was used to suppress relapse. Autoantibodies and circulating immune complexes were effectively eliminated regardless of their IgG subclass. CONCLUSION: Immunoadsorption onto protein A might be used as an extracorporeal treatment option in SLE when other therapies are ineffective.

Administration, Oral↗
PubMed1996

Therapy of Behçet's disease.

Behçet's disease (BD) is a multisystem vasculitis of unknown origin. In this retrospective study we analyzed the therapy of 32 patients seen between 1978 and 1993 at the Departments of Rheumatology, Ophthalmology, and Dermatology of the Tübingen University Clinic. The aim of this study was to evaluate the efficacy of different therapeutic strategies concerning different organ manifestations of the disease, especially eye disease. A total of 20 patients had cutaneous manifestations or arthritis. Whereas treatment with colchicine (Col), azathioprine (AZA), cyclosporine (CSA), or steroids (Ster) produced only partial remissions, a combination of CSA, AZA, and steroids led to complete remissions. Interferon-gamma (IFN-gamma) therapy led to remission rates of 60% (complete) and 20% (partial). In all, 22 patients had uveitis (posterior or panuveitis). Steroids were effective in only 50% of the patients and Col was partially effective in 66%. AZA induced a remission in 71% of cases and CSA was partial effective in 60%. The threshold combination of AZA, CSA, and Ster induced a complete remission in 66% of the patients. IFN-gamma was ineffective in 80%. IFN-alpha was used in one patient only and induced a complete remission. These results demonstrate that although our patient group is too small to allow significant conclusions to be drawn, in terms of the literature, for mucocutaneous disease and arthritis, IFNs might be the best therapy, whereas for uveitis as well as other more severe features of the disease, CSA or AZA + Ster should be used. If the latter are ineffective, the threefold combination (AZA, CSA, Ster) is probably the most effective alternative. The significance of IFN-alpha will be evaluated in further studies.

Azathioprine↗
PubMed1996

Treatment of hormone-refractory prostate cancer with 90Y-CYT-356 monoclonal antibody.

A Phase I dose-escalation study using 90Y-CYT-356 monoclonal antibody was performed in 12 patients with hormone-refractory prostate carcinoma. Biodistribution studies using 111In-CYT-356 were performed 1 week before 90Y-CYT-356 administration. Of the 12 patients, 58% had at least one site of disease imaged after administration of 111In-CYT-356. The dose of 90Y ranged from 1.83-12 mCi/m2. Both 111In and 90Y-CYT-356 were tolerated well, without significant nonhematological toxicity. Myelosuppression was the dose-limiting toxicity and occurred at dose levels of 4.5-12 mCi/m2. Of the patients receiving </=9 mCi/m2, 55% had grade 1 or 2 leukopenia and/or thrombocytopenia. Two of three patients treated with 12 mCi/m2 experienced grade 3 thrombocytopenia and leukopenia. One patient treated with 12 mCi/m2 had grade 4 neutropenia. The maximum tolerated dose of 90Y-CYT-356 was 9 mCi/m2. Only one patient developed a human anti-mouse antibody 4 weeks after treatment. No patient attained a complete or partial response based on prostate-specific antigen and/or radiological criteria. Three patients had transient subjective improvement in the symptomatology of their disease. In addition, patients treated with 12 mCi/m2 of 90Y-CYT-356 had a slightly longer freedom from disease progression than patients treated with doses of 90Y-CYT-356 </=9 mCi/m2.

Aged↗
PubMed1995

[Cogan I syndrome: too often detected too late? A contribution to early diagnosis of Cogan I syndrome].

BACKGROUND: Cogan's syndrome is an uncommon disease characterized by ocular inflammation, vestibuloauditory dysfunction and symptoms of systemic disease. The etiology is unknown, however there is evidence for an autoimmune pathogenesis. The "typical" Cogan's syndrome presents as bilateral interstitial keratitis and progressing vestibuloauditory dysfunction. The presence of other inflammatory manifestations in addition of keratitis has been termed as "atypical" Cogan's syndrome. PATIENTS: We report on six patients presenting with typical as well as atypical ocular manifestations between 1982 and 1994. Typically, the illness was accompanied by systemic symptoms. Each patient had audiovestibular involvement, that was the initial presentation in 4 cases. Vestibular dysfunction often preceded hearing loss. Five of our patients not only presented with keratitis but also demonstrated signs of ocular inflammation diagnosed as scleritis or episcleritis. In two patients these ocular symptoms were the first signs of Cogan's syndrome, recurred periodically and did not respond to corticosteroids. RESULTS: In 3 patients that were diagnosed early and treatment with corticosteroids was initiated early, hearing could be stabilized, in the remaining patients total bilateral deafness could not be prevented. CONCLUSION: The importance of being aware that vestibuloauditory dysfunction may occur in patients with ocular inflammation, and the fact that early immunotherapy may prevent the risk of deafness, has to be emphasized.

Adolescent↗
PubMed1995

Behçet's disease: epidemiology and eye manifestations in German and Mediterranian patients.

Behçet's disease (BD) is a systemic disease of unknown etiology, characterized by multiple organ involvement. Although its incidence is high in the Mediterranean countries and in Japan, BD is not often found in German patients. We therefore compared the epidemiological and clinical involvement of BD in 39 patients of German and of Mediterranean origin. The first manifestation was oral aphthosis in 72% of patients, followed by eye involvement (62%), skin lesions (25%), and arthritic problems (23%). Eventually, all our patients developed oral aphthosis. Whereas Germans had eye involvement in only 55% of cases (Mediterraneans, 71%), they came up with venous thrombosis or thrombophlebitis more often (64%) as compared with Mediterraneans (29%). The first ocular symptom was anterior uveitis in 87.5% of patients; the visual prognosis was poor due to occlusive retinopathy. Among 22 eyes of 12 patients, 16 had a visual acuity of 0.1 or less after 5 years of disease. We found a similar association with human leukocyte antigen B5 (HLA-B5) in the German patients (66.7%) and in the Mediterranean group (54.4%). There was no significantly higher HLA-B5 association with the uveitis or arthritis type. These results demonstrate a few differences between the two ethnic groups but illustrate that in Germans the disease also has a poor prognosis.

Adolescent↗
PubMed1994

Immunology of the eye and the joint.

It is well known that polyarticular joint diseases such as rheumatoid arthritis, HLA-B27-associated arthritis and Borreliosis can be associated with eye diseases, such as uveitis, scleritis and keratitis. However, the mechanisms underlying the involvement of these tissues remain unclear. A recent meeting examined the immunoregulation of the eye and the joint in an attempt to determine their similarities and differences.

Animals↗
PubMed1994

Two-dimensional cryostat section electrophoresis: a novel method and its application to the diseased synovial membrane.

A two-dimensional electrophoresis technique for analysing sections of human tissue is described. Cryostat sections, 10 microns thick, are placed on an isoelectric focusing gel and then transferred to an SDS gel in the second dimension. The protein pattern is visualized by silver staining and is thought to represent soluble proteins. The silver-stained proteins were found to be both reproducible and, to the extent tested, organ-specific. This method was used to analyse 43 synovial membranes from patients suffering from rheumatoid arthritis or degenerative joint diseases. The analysis did not reveal any specific protein pattern for rheumatoid arthritis. The protein spot number was not related to the cause of arthritis. However, the total protein spot number was related to the histomorphological synovitis type, with those exhibiting either an exudative or proliferative synovitis pattern possessing significantly higher protein spot numbers than those specimens exhibiting a sero-fibrous or lympho-plasmacytic pattern of synovitis.

Arthritis, Rheumatoid↗
PubMed1993

13C NMR investigation of synovial fluids.

13C NMR spectra of synovial fluids from 20 patients suffering from rheumatic diseases have been recorded. Structural changes in hyaluronic acid, the main carrier of the viscoelastic properties of synovial fluid, could be observed in the NMR spectra of the native biological fluid. By comparing these spectra with those of purified hyaluronic acid, a rough estimation of the degree of depolymerization of synovial hyaluronic acid was possible. The patients with rheumatoid arthritis appeared to have a lower degree of polymerization compared to patients with osteoarthrosis. Thus, 13C NMR spectroscopy provides useful information about biophysical properties of synovial fluid.

Arthritis, Rheumatoid↗
PubMed1992

Primary splenic presentation of plasma cell dyscrasia: report of two cases.

Primary splenic presentation of plasma cell tumors is extremely rare. Recently we observed two female patients with primary (initially solitary) plasmacytoma of the spleen. While the pathoanatomical diagnosis of plasmacytoma could be established easily, the clinical picture in both cases was puzzling and allowed no definitive diagnosis to be made. One of the patients exhibited a long-standing monoclonal gammopathy. Repeated bone marrow examinations in both patients revealed slight increase in plasma cells (between 5 and 10% of all nucleated cells), but no infiltrates of multiple myeloma. The leading clinical feature in both cases was pronounced splenomegaly (780 g and 1600 g). Histologically both spleens exhibited marked infiltration by pleomorphic plasma cells, with monotypic expression of IgG kappa in one case and of the light chain lambda in the other. A broad panel of monoclonal antibodies detecting various hemopoietic and nonhemopoietic antigens was used to determine the immunophenotype of the neoplastic plasma cells, but in both cases they reacted only with a minority of the antibodies applied. The bone marrow in both cases remained free of tumorous infiltrates, but the disease progressed a few months after splenectomy with infiltration of the liver in one case and of lymph nodes in the other. To summarize, these two cases are definitely not multiple myelomas but could represent a distinct entity among the plasma cell dyscrasias for which the preliminary term "disseminated plasmacytoma with primary splenic presentation" is proposed.

Adult↗
PubMed1990

Inhibition of human phospholipases A2 by cis-unsaturated fatty acids and oligomers of prostaglandin B1.

Inhibition of human phospholipases A2 by cis-unsaturated fatty acids and their oxidative metabolites and/or polymers was studied using partially purified human phospholipases A2 and [1-14C]oleate labelled, autoclaved E. coli as substrate. As previously reported for other phospholipases A2, oleic and arachidonic acids inhibited human synovial fluid phospholipase A2 with IC50s of 15 and 30 microM respectively. Air oxidation of arachidonic acid or hydroxylation of oleic acid (12-hydroxy-oleate) substantially relieved that inhibition. Similarly, the enzymatically oxidatized metabolite of arachidonate, prostaglandin B1 (PGB1), did not inhibit enzymatic activity. However, prostaglandin Bx (PGBx), an oligomer (n = 6) of PGB1, was a potent inhibitor of Ca(++)-dependent, neutral-active phospholipase A2 activities. Enzymatic activity in acid extracts from human neutrophils, platelets, sperm, plasma, synovial fluid, endometrium, degenerative disc, and snake venom was inhibited by PGBx with IC50s ranging from 0.5-7.0 microM. Inhibition was independent of substrate phospholipid concentration over a 24-fold range (5-120 microM) and PGBx quenched the tryptophan fluorescence of snake venom phospholipase A2 in a dose-dependent manner. Agonist-induced (A23187) release of arachidonic acid from prelabelled human neutrophils and cultured human endothelial cells was also inhibited by PGBx with IC50s of 3 and 20 microM, respectively. These results illustrate that oxidative reactions of cis-unsaturated fatty acids relieve their natural inhibitory activity, and polymerization of an inactive fatty acid metabolite yields a potent inhibitor of in vitro and in situ phospholipase A2 activity.

Arachidonic Acid↗
PubMed1990

[Quantitatively evaluated magnetic resonance tomography as a therapeutic follow-up of the nonsteroidal antirheumatic ademetionin: a pilot study in patients with gonarthrosis].

The report deals with a double-blind study of nine patients treated over a period of three months with either ademetionin (five patients) or with a placebo (four patients). Prior to treatment, and after three months, clinical and biochemical studies were carried out as well as radiological examinations and MRT. The latter had been standardised previously in order to obtain a cartilage signal which could be quantified. Of the five patients treated with ademetionin, none were improved clinically, two were worse and three were unchanged, but on MRT, three were improved, one was worse and one was unchanged. Amongst the placebo patients, the clinical results were: three improved, none worse and one unchanged, with similar findings on MRT. MRT appears to be useful for complementing the information for treatment planning with chondroprotective drugs.

Adult↗
PubMed1990

Quantitative evaluation of hyaline cartilage disorders using flash sequence. I. Method and animal experiments.

A method for quantitative evaluation of hyaline cartilage signal intensities has been developed in an experimental study of 6 swine knees with different types of arthritis. A FLASH sequence with TR 50 ms, TE 10 ms and flip angles of 5, 10, 20, 25, 30, 35, 50 and 90 degrees was employed. Two parameters of the signal intensity flip angle curves proved to be useful for tissue characterisation: The initial increase (A) and the maximum (M).

Animals↗
PubMed1990

Quantitative evaluation of hyaline cartilage disorders using flash sequence. II. Clinical applications.

In a prospective clinical study 24 normal volunteers and 106 patients with acute and chronic arthritis, osteoarthritis and post-traumatic alterations of the knee joints were examined. Using the parameters A and M 98 per cent of the pathologic cartilages and 74 per cent of the normal cartilages could be identified. In addition 78.5 per cent were correctly categorized in 5 cartilage classes. The A/M classification proved to be a fast and specific method for evaluation of cartilage disorders with special promise for follow-up examinations during therapy.

Adolescent↗
PubMed1989

[Pancytopenia during low-dose oral methotrexate therapy of psoriatic arthritis].

Pancytopenia and interstitial pneumonia occurred in a 70-year-old woman with psoriatic arthritis and compensated renal insufficiency while she was being treated with low doses of the folic-acid antagonist methotrexate (5 mg weekly). Despite the administration of platelets, red blood cells, antibiotics, acyclovir and folinic acid (100 mg daily), the pneumonia progressed, and the patient died of global respiratory failure.

Administration, Oral↗